Morin, a bioflavonoid abundant in Morus alba (Moraceae) and traditionally used in Ayurveda and Chinese medicine for the treatment of convulsions and inflammation, modulates neuroinflammatory pathways relevant to epilepsy. This study investigated the effects of morin on inflammasome-associated neuroinflammation, assessed using downstream markers such as caspase-1 and IL-1β, in a rotenone-lamotrigine-PTZ-induced model of drug-resistant epilepsy (DRE). Drug resistance was established through chronic co-administration and confirmed by non-responsiveness to carbamazepine and valproate. Morin (20 and 40 mg/kg), alone or in combination with valproate, was evaluated against vigabatrin for its impact on seizure severity, neurochemistry, and neuropathology. Morin dose-dependently reduced seizure scores and partially normalized whole-brain glutamate and GABA levels, with the 40 mg/kg morin-valproate combination most effectively restoring the glutamate: GABA ratio. Additionally, morin-based treatments reduced caspase-1, IL-1β, and NQO1 levels in the hippocampus and cortex, improved neuronal architecture, and attenuated microglial and astroglial activation. These findings suggest that morin may be a promising adjunctive candidate for DRE by modulating seizure severity, excitatory-inhibitory imbalance, oxidative stress, and inflammation associated with inflammasome-linked signaling.

Epilepsy is a chronic neurological disorder characterized by recurrent unprovoked seizures, generally associated with an imbalance of neurotransmitters, neuroinflammation, and oxidative stress. Formononetin, a naturally occurring isoflavone found in several medicinal plants, has been previously explored for its anti-inflammatory and antioxidant effects in preclinical studies. These properties suggest a possible role of formononetin in modifying the pathological pathways underlying epilepsy. Pentylenetetrazol (PTZ)-induced kindling is one of the most reliable animal screening models for exploring the anti-epileptic potential of investigational natural compounds, such as formononetin, enabling its examination in reducing seizure susceptibility and severity in the mouse model. This study evaluates the anticonvulsant efficacy of formononetin by modulating neuroinflammation in a pentylenetetrazol-induced kindling mouse model. Male and female mice were divided into five groups: naïve, Negative control (PTZ-kindled), positive control (sodium valproate 200 mg/Kg), and PTZ + formononetin (10 mg/kg, 20 mg/kg, and 40 mg/kg). PTZ was administered at a dose of 40 mg/kg every alternate day, followed by assessment of seizure severity score using the Racine scale. Neuroinflammatory biomarkers (IL-1β, NF-κB) and neurotransmitter levels (GABA, Glutamate) were measured. Histopathology was performed to identify the morphological changes in the brains of mice following treatment. Formononetin exhibited dose-dependent anticonvulsant and neuroprotective effects in the PTZ-kindling mouse model, reducing seizure severity, improving motor coordination, and easing anxiety-like symptoms. It restored the glutamate–GABA balance, suppressed NF-κB and IL-1β expression, and preserved neuronal integrity, underscoring its potential as a multi-target therapeutic agent for epilepsy through modulation of neurotransmission and neuroinflammation.

Aluminum, a widely occurring environmental metal, has been implicated as a neurotoxic agent and is associated with the development of several neurodegenerative conditions, including Alzheimer’s disease (AD). Its neurotoxicity is largerly attributed to the induction of oxidative stress , which exacerbates neuroinflammation, leading to cognitive deficits and progressive neuronal dysfunction. Trans-anethole (TA) possesses diverse pharmacological activities, including anti-inflammatory, antioxidant, antifungal, and anticancer effects. However, its neuroprotective potential against AlCl₃-induced neurodegeneration, particularly in the context of memory impairment mediated by inflammation and oxidative stress, remains unknown. Therefore, this study was conducted to evaluate the potential role of TA in mitigating neurodegeneration. To establish an aluminum-induced neuroinflammation-associated neurodegenerative model, rats received oral administration of 150 mg/kg AlCl₃ for 90 days. TA was administered at three different dosages between days 31 and 90: 40, 80, and 160 mg/kg between days 31 and 90. Cognitive performance was assessed using the Morris water maze (MWM) and passive avoidance test (PAT). Neuroprotective effects were evaluated by analyzing acetylcholinesterase (AChE) activity, oxidative stress markers (catalase, glutathione, and malondialdehyde levels), and neuroinflammatory mediators (NLRP3 inflammasome, Interleukin-1β, and TNF-α) in AlCl₃-exposed rats. TA significantly mitigated aluminum-induced neuronal damage by restoring antioxidant defence, inhibiting AChE activity, and downregulating inflammatory proteins, including NLRP3, TNF-α, and IL-1β. Histopathological analysis further confirmed its neuroprotective role. The findings of this study suggests that TA holds therapeutic potential for neurodegenerative disorders by mitigating memory deficits, neuroinflammation, and oxidative stress. Aluminum (150 mg/kg) induced AD-like neurodegenerative conditions in rats. TA (40–160 mg/kg) showed dose-dependent neuroprotection in AlCl3-exposed rats. TA improved memory and learning in rats assessed by MWM and PAD test. TA reduced oxidative stress, reduced neuroinflammation, and inhibited AChE activity. Histological analysis of cortex and hippocampus confirmed neuronal preservation in TA-treated groups.

Atherosclerosis and Alzheimer's Disease are two significant health concerns characterised by overlapping pathophysiological mechanisms, including chronic inflammation, oxidative stress, and lipid metabolism dysregulation. Impaired vascular integrity in atherosclerosis enhances the accumulation of Aβ plaque in the brain by reducing cerebral perfusion and compromising the clearance of Aβ. This review examines the shared pathways linking these conditions, emphasizing the role of the NLRP3 inflammasome, Receptor for Advanced Glycation End Products, and the apolipoprotein E4 allele in exacerbating vascular dysfunction that promotes neurodegeneration. The interplay between these factors underscores the potential of targeting these common pathways as a therapeutic strategy for both diseases. In preclinical studies, emerging treatments, NLRP3 inflammasome inhibitors like MCC950 and CY-09, show promise in mitigating both arterial plaque formation and neuronal amyloid deposition, while innovative microRNA-based therapies targeting miR-146a and miR-155 offer novel approaches to reduce inflammatory responses. Additionally, modulation of lipid metabolism through liver X receptor agonists like T0901317 and cholesteryl ester transfer protein inhibitors, including Anacetrapib, offers potential dual benefits for cardiovascular and neurological health. However, challenges such as restricted BBB permeability, genetic and sex variability, and limited long-term clinical evidence continue to constrain the effectiveness of dual-targeted therapeutic approaches. Future perspectives suggest integrating multi-- modal therapies that combine anti-inflammatory, lipid-regulatory, and antioxidant strategies to effectively address these interrelated diseases. Advancements in molecular biology and imaging techniques may facilitate the development of personalised medicine approaches, ultimately improving outcomes for patients suffering from both atherosclerosis and Alzheimer's Disease.

The rotenone adjuvant kindling paradigm replicates key clinical features of drug-resistant epilepsy (DRE), including broad-spectrum pharmacoresistance, neuroinflammation, and oxidative stress, by combining mitochondrial complex I inhibition with pentylenetetrazol (PTZ) or corneal kindling. PTZ, a GABAA receptor antagonist, induces seizures by reducing inhibitory neurotransmission and is widely used to model kindling and seizure susceptibility; in this paradigm, its repeated subconvulsive dosing facilitates progressive epileptogenesis and enhances network hyperexcitability. Rotenone-induced microglial activation and mitochondrial dysfunction further potentiate PTZ sensitivity, limiting the penetration and effectiveness of antiseizure drugs by promoting cytokine release, disrupting the blood–brain barrier, and overexpressing efflux transporters. In comparison to traditional DRE models, this paradigm’s construct, face, and predictive validity are strengthened by its recapitulation of neuropsychiatric comorbidities and spontaneous recurrent seizures. Comparative findings suggest greater clinical relevance and improved suitability for evaluating mechanism-based therapies targeting mitochondrial dysfunction, GABAergic imbalance, and inflammatory signaling; however, concerns regarding systemic toxicity, mortality, and inter-animal variability remain important limitations. Overall, the rotenone adjuvant PTZ-kindling model represents a promising, though imperfect, translational platform for the development of novel therapies for DRE.

Drug-resistant epilepsy (DRE) is a substantial medical challenge due to the scarcity of effective therapies. Newly identified mechanisms, such as mitochondrial dysfunction and the Nod-like receptor protein (NLRP3) inflammasome activation, are implicated in playing an important role in the pathogenesis of DRE. Mitochondria are crucial for maintaining neuronal energy balance and cell viability. The NLRP3 inflammasome is triggered when mitochondria are damaged, releasing reactive oxygen species (ROS) and mitochondrial DNA. This activation leads to a cascade of pro-inflammatory reactions, exacerbating neuronal damage and seizures. This review highlights the proposed molecular mechanism involving the interplay of mitochondrial impairment with precipitated NLRP3 inflammasome activation in DRE. It also explores the possibility of implementing drug-delivery techniques to deliver antiseizure medications (ASMs) with agents reversing mitochondrial damage as a novel approach to treat DRE. These advanced delivery methods might improve the efficacy of ASMs, aid in overcoming drug resistance observed in epilepsy, and thus offer a promising means of ameliorating seizure activity in DRE.

The nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome pathway, involving NLRP3 protein and caspase-1, is reported to be involved in the progression of epilepsy into drug-resistant epilepsy (DRE). Overactivation of ABC transporter proteins in neuronal cells as a result of NLRP3 activation leads to the efflux of the anti-seizure medications, rendering them ineffective. This work aims to identify novel hit molecules that can halt neuroinflammation as well as potentiate the action of anti-seizure medications. Initially, molecular docking studies evaluated procyanidin binding against NLRP3, caspase-1, and ABC proteins as -177.001, -126.842, and -143.671. Procyanidin was further subjected to MD simulations for 100 ns, revealing RMSD values below 5 Å for procyanidin in complex with ABC and caspase proteins, whereas with NLRP3, it was below 2.5 Å. Procyanidin showed a ΔG binding value of -82.10142857 ± 15.07 with caspase, -61.9005 ± 9.95 with NLRP3, and -101.021 ± 5.27 kcal/mol with ABC protein. Procyanidin was predicted to bear good plasma-protein binding and a class 5 acute toxicity class ligand. It also showed a band energy gap of -4.873 eV, which suggested its stability.

Age-related Macular Degeneration (AMD) is a severe eye illness that is going to lead in the race for incurable blindness globally among the elderly population. AMD is the third common reason responsible for affecting the quality of life globally. The macula and the retinal layers are adversely affected during AMD and are responsible for the loss of vision eventually. Numerous genetic variables, lipid metabolism, ageing and oxidative damage are the causative factors in the genesis of AMD. Lack of antioxidants, smoking and excessive alcohol intake contribute to increasing the risk of AMD. Management of dry AMD involves the use of nutritional supplements like zinc and antioxidants, along with conventional treatment, however, the use of nutritional supplements can only give minor benefits on the progression of dry AMD. Later stages of AMD need to be managed by cell-based interventions where the damaged or lost cells are replaced with fresh donor cells. A plethora of treatment methods are used in the management of AMD, such as nutrition, antibody-based treatments, stem cell management and nanotherapeutics. The available expensive treatments come with a number of adverse effects and future developments require the involvement of risk factor modification approaches, personalized therapy, targeting the disease specific pathways, exploring better anti-vascular endothelial growth factor (VEGF) inhibitors and many other regenerative approaches, that will broaden techniques to diagnose, control and treat AMD. This review provides an overview of the progression of AMD and the causative factors, with considerable emphasises on the current and potential prospects.

Over 70 million people worldwide suffer from epilepsy, a persistent brain disorder. Although there are more than 20 antiseizure drugs available for the symptomatic treatment of epilepsy, about one-third of patients with epilepsy experience seizures that show resistance to pharmacotherapy. Since patients with drug-resistant epilepsy are more prone to physical injuries, psychosocial dysfunction, early death, and deteriorated life quality, the development of safer and more effective treatments is a crucial clinical need. The gut-brain axis and microbiome research advances have provided new insights into the pathophysiology of epilepsy, the resistance to anti-seizure medicine, and potential treatment targets. Inflammation, disturbance of the blood-brain barrier, and altered neurotransmitters are key pathways linked to gut dysbiosis. The characterization of microbial species and functional pathways has advanced thanks to metagenomic sequencing and high-throughput analysis. In this review, we elaborate on the gut-mediated molecular pathways involved in drug-resistant epilepsy, the gutmodulatory therapeutic options, and their combination with antiseizure medications for drug-resistant epilepsy.

Background Several studies have shown that the ketone bodies produced by consumption of the ketogenic diet can be useful in the long-term treatment of several neurological conditions namely epilepsy, glioblastoma multi-forme, autism, Parkinson’s disease, traumatic brain injury, Alzheimer’s disease, migraine and multiple sclerosis. The review discusses each condition based on the global incidence, risk factors, pathophysiology, influence of the ketogenic diet on the disease and how the ketogenic diet can be used in the management of the disease. Method Literature search was done for the use of ketogenic diet on neurological disorders from the year 1990-2022 using three databases: Pubmed, Google Scholar and Science Direct. Results Ketone bodies have the underlying ability to trigger favorable mechanisms in the body - such as energy compensation to the neurons during cell necrosis or apoptosis, elevated GABA mediated inhibition, improved blood flow in the cerebrum, a positive influence in the Microbiota-Gut-Brain Axis (MGBA) system, protection against oxidative stress by increasing the concentration of anti- oxidants, stabilization of ion channels and membrane potential, reduction in neuro-inflammation, increased neuroprotection and lastly increased respiratory rate and ATP production which contributes to energy efficiency that helps to rectify the metabolic imbalance and maintain a balance between the excitatory and inhibitory neurotransmitters in the brain. Conclusion The ketogenic diet can potentially act as a significant tool for symptomatic treatment of life threatening and long-term neurological ailments. Going forward, it could also aid in the curing of such conditions.

Glaucoma is one of the widely prevalent ophthalmological conditions responsible for extreme clinical outcomes like loss of vision. This necessitates the need for proper therapeutic management of the condition. Although a number of treatment paradigms are being practiced by clinicians, they are marred by limited success in management. The primary reason behind the partial efficacy and success is owing to the nonadherence and insufficient concentrations at the target sites. Nanotechnology has demonstrated its competencies to alleviate the therapeutic limitations of multiple classes of drugs. Nanocarrier-based delivery of antiglaucoma agents can be leveraged to enhance the bioavailability, site-specific targeting, and controlled drug release. These benefits can ultimately translate to better therapeutic modalities to combat glaucoma. The chapter delves into the intricacies of polymeric and lipid nanocarriers for glaucoma management.

This chapter discusses the pathophysiology of wound healing, current studies on nanoherbal formulations in wound healing, and different techniques for the preparation and evaluation of nanoformulations. Topical treatments, such as antibacterial or colloidal agents, are used in the conventional technique of wound management to prevent infection and promote a good healing process. Nanotechnology investigates submicroscopic particles and related phenomena (100 nm). Metal nanoparticles (such as silver, gold, and zinc) are being used increasingly often in dermatology due to their beneficial influence on wound healing as well as treating and preventing bacterial infections. A constantly moist wound environment, ease of use, and fewer dressings are further benefits. Thus, nanoformulations are better than conventional dosages for wound healing, due to enhanced bioavailability and permeability, better control release mechanisms, enhanced therapeutic efficacy, and reduced toxicity. Antioxidant and antiinflammatory activities are additional wound-healing mechanisms displayed by these nanoformulations.

Herbal medicines have been utilized as the foundation of healthcare from the dawn of humanity and are still frequently used today. The significance of their therapeutic, pharmacological, and economic usefulness is still being recognized, but it differs greatly by country. In the case of medicinal plants, legislative controls have not emerged around a structured control paradigm. The absence of scientific and clinical evidence, as well as a greater understanding of the efficacy and safety of herbal products, is a key impediment to the incorporation of herbal medications into modern medical procedures. Despite a significant increase in herbal medicine research worldwide, a lot of clinical investigators and even members of ethics committees have reservations about dealing with relevant ethical issues. In this article, we attempt to focus on clinical, ethical, and regulatory issues of botanicals.

The etiologies of several cardiovascular, inflammatory, neurological, hereditary disorders, cancer, and infectious diseases have implicated changes in the genetic set up or genetic mutations as the root cause. Nucleic acid based therapeutics (NBTs) is a new class of biologics that are known to regulate gene expression at the transcriptional and post-transcriptional level. The NBTs include oligonucleotides, nucleosides, antisense RNA, small interfering RNAs, micro RNA etc. In recent times, this new category of biologics has found enormous potential in the management of cardiovascular, inflammatory, neurological disorders, cancer, infectious diseases and organ transplantation. However, the delivery of NBTs is highly challenging in terms of target specificity (intracellular delivery), mononuclear phagocyte system uptake, stability and biodistribution. Additionally, management of the above mentioned disorders require regular and intrusive therapy making non-invasive routes preferable in comparison to invasive routes like parenteral. The nasal route is garnering focus in delivery of NBTs to the brain in the management of several CNS disorders due to the associated merits such as non-invasiveness, possibility of chronic delivery, improved patient compliance, avoidance of hepatic and gastrointestinal metabolism as well as ability to bypass the BBB. Hence in recent times, this route has been sought by the reserachers as an alternative to parenteral therapy for the delivery of several NBTs. This review shall focus on an array of NBTs delivered through nasal route, their challenges, applications and opportunities. The novel delivery systems for incorporating NBTs; their targeting strategies shall be critically reviewed. The challenges towards regulatory approvals and commercialization shall also be discussed at large. Comparison of learnings derived from the success and barriers in nasal delivery of NBTs will help in identification of futuristic opportunities for their translation from bench to bedside.

Diabetic retinopathy is one of the most prevalent complications of diabetes affecting a large number of people worldwide. Triphala churna - an Ayurvedic formulation consisting of powder of three fruits, Emblica officinalis, Terminalia bellirica and Terminalia chebula has potent antioxidant and anti-diabetic properties. Hence, the study was designed to evaluate the effect of Triphala churna in diabetic retinopathy. Diabetes was induced in rats with streptozotocin (55 mg/kg, i.p.). After four weeks of induction, animals were treated with Triphala churna powder mixed in a vehicle at a dose of 250, 500, and 1000 mg/kg for the next four weeks. At the end of the study, plasma glucose, lactate dehydrogenase levels were determined. Sorbitol dehydrogenase, aldose reductase, and oxidative stress parameters were determined in lens tissues. Electroretinography was carried out. Histopathology study of the retina was studied at the end of the study. Triphala churna significantly reduced plasma glucose and lactate dehydrogenase levels. Triphala significantly reduced sorbitol dehydrogenase, aldose reductase, and oxidative stress in lens tissues. Furthermore, Triphala significantly increased 'a' wave and 'b' wave amplitude with a reduction in the latencies. The retinal thickness was significantly reduced in Triphala-treated animals. From the results, it can be concluded that Triphala churna delays the progression of retinopathy in diabetic rats.

Gasdermins are novel pore forming proteins that comprise Gasdermin A, Gasdermin B, Gasdermin C, Gasdermin D, Gasdermin E and Pejvakin (DFNB59). Recently, pyroptosis has been redefined as "Gasdermin mediated necrosis", as gasdermins are key regulators of apoptosis, necrosis, and pyroptosis. The discovery of the gasdermin family has broadened the field of pyroptosis studies. Studies have correlated gasdermins with several diseases. This review summarizes the physiological roles and signal transduction of gasdermins. It further highlights the role of gasdermins in pathological conditions like autoimmune disease, kidney diseases, and central nervous system diseases.

Objective:Ischemic stroke is one of the leading causes of disability in adults worldwide. The present study was aimed to evaluate the efficacy of Narirutin-rich fraction (NRF), obtained from grape fruit peel, on cerebral ischemia/reperfusion injury in rats. Methods:Male Wistar rats (180-200 g) were subjected to bilateral carotid artery occlusion for 30 min followed by reperfusion for 24 h to induce cerebral ischemia/reperfusion injury. NRF (150, 300 mg/kg, oral) was administered for 7 days continuously before animals were subjected to ischemia/reperfusion injury. Various behavioral tests (for measurement of motor coordination, locomotor activity, and spatial memory), biochemical parameters (lipid peroxidation, superoxide dismutase, and catalase activity), and histopathological alterations were assessed. Results:Seven-day NRF (150 and 300 mg/kg) pretreatment significantly improved neurobehavioral alterations and histological findings as compared to the disease control group. Further NRF treatment significantly reduced oxidative damage as indicated by improved lipid peroxidation, superoxide dismutase, and catalase activity as compared to disease control animals. Conclusion:The present study demonstrated the protective effect of NRF against cerebral ischemia/reperfusion injury in rats. The results suggest that NRF can be a potential pretreatment option against cerebral ischemia/reperfusion injury.

Colorectal cancer (CRC) is the third common cause of cancer-related deaths globally. It begins nearly as a benign polyp and slowly develops into a malignant tumor. The normal colonic epithelium can get transformed into the dysplastic epithelium, leading to the formation of adenomatous polyps and ultimately colorectal cancer. Most colorectal cancers are localized with or without lymph node metastases. Cancer stem cells act as a clonogenic core in the colon for the genesis for new tumor growth. Colon cancer stem cells (CCSC) are the self-renewable, pluripotent cells that have an innate capacity to regenerate as well as initiate tumors. They are predominantly regulated by oxidative stress. Excessive production of reactive oxygen species (ROS) is known to promote the initiation and progression of cancer. Despite the current treatment strategies, there is a need to develop a new target for the treatment of colorectal cancer that offers a curative response to patients with advanced cancers. The new treatment modalities have been focusing on anti-CRC treatments that target the stem cell population to suppress tumor growth and cancer relapse. This chapter focuses on the implications of targeting colon cancer stem cells for the treatment of hypoxia-induced colorectal cancer.